The broad objectives of this research are to expand ongoing studies of the mechanisms and routes by which the Lyme disease (LD) spirochete, Borrelia burgdorferi (Bb), is maintained and distributed among wildlife and humans in a highly endemic area of the Far West; to further assess environmental factors that may place people at risk of acquiring Bb-infection or LD; and to determine the antiquity of Bb-infection in this region. Human risk of exposure to vector ticks along trails and in picnic areas will be compared with an ecological index of risk in several heavily-used recreational areas in northern California. Tick abundance will be quantified by flagging vegetation and by enumerating ticks that adhere to the clothing of a walker simulating a hiker. Infection rates will be determined by testing ticks with standard microbiological procedures. A follow-up seroepidemiologic study of a high-risk community (HRC) will be undertaken to discover if the presence of tick- or insect-specific IgG can be correlated with seroprevalence to Bb and self-reported exposure histories to arthropod bites; 3 assays will be performed including ELISA, SDS-PAGE and immunoblotting. Peridomestic exposure to Bb in the HRC will be evaluated by comparing the abundance of, and spirochetal infection rates in, vector ticks and anthropophilic bloodsucking flies collected around the homes of LD victims vs. non-victims. The ability of 2 species of hard ticks (Ixodes spp.) and the western cone-nose bug to acquire, maintain, and transmit Bb will also be determined using rodents as experimental hosts. Further, the concept that each of the 3 species of North American relapsing fever spirochetes is confined to one species of soft tick will be reevaluated because of geographic overlap with Bb. Fresh isolates of all 3 Borrelia spp. will be characterized molecularly to determine if they are indeed specifically distinct, and the vector competence of each of their soft tick vectors (Ornithodoros spp.) for all 3 spirochetes and for Bb will be studied. Field and laboratory studies will be carried out to fill-in some basic gaps in knowledge concerning the life histories of 2 important western vectors of Bb, Ixodes pacificus and Ixodes neotomae, especially the former. Information gleaned from these studies will be used to model the population dynamics of Ixodes pacificus. Finally, 3 kinds of archival museum specimens (ticks, woodrat skins, Native American skeletal remains) will be assayed for Bb-nucleic acid with the polymerase chain reaction to determine the antiquity of LD in this region.